The overall long term objective of our research effort is to define the roles of selected energy-yielding fuels in energy homeostasis of normal, fasting and diseased humans. The current specific aim is to identify the importance of ketone body metabolism in fasting humans with special emphasis on acetone. Acetone is produced endogenously at appreciable rates in fasting and diabetic humans and the major mechanism of acetone disposal is in vivo metabolism. The pathways by which acetone is metabolized are unclear. Using gas chromatographic techniques, two new metabolites of acetone, acetol and 1,2-propanediol, have been identified in the blood stream of fasting and diabetic humans. Using relative non-invasive isotope tracer techniques, the rates of acetone, acetol and 1,2-propranediol metabolism will be quantified in fasting humans. Acetonemic rats and dogs, produced by placing acetone in the drinking water of the animals, are being utilized to study aspects of metabolism which cannot be done in humans.